Growth hormone evokes a variety of biological responses in mammals in vivo and in excised tissue studied in vitro. Initial responses of adipose tissue from hypophysectomized rats are insulin-like and include increased glucose uptake and utilization increased amino acid oxidation and antagonism of the fat mobilizing effects of ephinephrine. Several hours later these effects disappear or reverse and the tissues become refractory to insulin-like stimulation by growth hormone. Using iodinated hormone, it is proposed to study binding of hormone to receptors in responsive and refractory tissue and to correlate receptor binding properties with biological responses. Modified growth hormone preparations will be studied to evaluate the nature of the hormone that interacts with the receptor. Another aspect of the study will examine the biochemical bases for the insulin-like response and will evaluate hormone related changes in the cyclic AMP system and in protein kinase activity. Increased leucine oxidation will be studied as an example of a growth hormone response that might occur in a cell free system and thus allow evaluation of hormone induced changes in the intracellular millieu. Possible inhibition of pyruvate dehydrogenase will be investigated as a possible cause of the late inhibition of glucose utilization.